Monteiro-Riviere ,NA. Indirect Immunohistochemistry

Monteiro-Riviere ,NA. Indirect Immunohistochemistry and immunoelectron microscopy distribution
of eight epidermal-dermal junction epitopes in the pig and in isolated perfused skin treated with bis
(2-chloroethyl) sulfide. Toxicologic Pathology 23:313-325, 1995.

Monteiro-Riviere NA: Integument. In Eurell J, Frappier B, eds. Dellman’s Textbook of
Veterinary Histology, Blackwell Publishing, Ames, Iowa, 6 th ed., pp.320-349, 2006.

Experimental Model Systems

• Practicality
• Absorption
Animal Models
• Toxicology - Increased absorption compared to man to
assess worse case scenario
• Rats, Mice, Rabbits
• Pharmacology - Similar absorption to man
• Toxicity
• Pigs, Primates, Hairless Rodents
• Immunological considerations
• Rabbits, Guinea Pigs, Rodents
• Species differences for different mechanisms are
independent ∴one species is not the best model for all
endpoints in humans!

Species Differences
• Anatomical factors such as thickness,
adnexial structures, etc.
• Biochemical differences in lipid
composition, enzymes, etc.
• Different receptors for immunological or
pharmacological agents
• Physiological differences including blood
flow, etc.

Body Site Differences
• The rate of penetration and absorption differs
across various body sites
• Scrotum > Forehead > Axilla > = Scalp > Back =
Abdomen > Palm and Plantar surface
• Seen in humans and animals making route to
route extrapolations “interesting.”
• The major reasons are due to:
– Differences in anatomy:skin thickness
– Differences in physiology: blood flow and distribution
of blood vessels
– Stratum corneocyte cell size ?

Pig Skin is Similar to Human Skin
• Similar surface characteristics
• Body masses and skin to body surface area ratio
• Sparse hair coat
• Thick epidermis
• Hair follicle density
• Epidermal turnover kinetics
• Lipid composition
• Biophysical properties of lipid
I like pigs. Dogs look up to us.
Cats look down on us.
Pigs treat us as equals.
Don’t use skin from an abattoir if hide is scalded!

Differences Between Pig and
Human Skin
• Pig skin has an additional interfollicular
muscle
• Young pigs have hair follicles that occur
in a triad
• Pigs have only apocrine sweat glands over
most of the body
• Immunological and drug metabolism
differences not well characterized

Monteiro-Riviere, NA. Comparative Anatomy, Physiology, and Biochemistry
of Mammalian Skin . In Hobson DW (ed) Dermal and Ocular Toxicology:
Fundamentals and Methods, Boca Raton, FL, CRC Press, Chpt. 1, 3-71, 1991.

Porcine Skin
Stromberg MW, Huang YC, Monteiro-Riviere NA. Interfollicular smooth muscle in the
skin of the domesticated pig. The Anatomical Record 201:455-462, 1981.

Porcine Skin

Human Skin

Monkey Skin

Nude Guinea Pig Skin

Mouse Skin

Nude Mouse

Rat Skin

Rabbit Skin

Cow Skin

Cow Skin

Dog Skin
Monteiro-Riviere NA: Integument. In Eurell J, Frappier B, eds. Dellman’s Textbook of
Veterinary Histology, Blackwell Publishing, Ames, Iowa, 6 th ed., pp.320-349, 2006.

Dog Skin
Monteiro-Riviere NA: Integument. In Eurell J, Frappier B, eds. Dellman’s Textbook
of Veterinary Histology, Blackwell Publishing, Ames, Iowa, 6 th ed., pp.320-349, 2006.

Cat Skin

Cat Skin
Monteiro-Riviere NA: Integument. In Eurell J, Frappier B, eds. Dellman’s Textbook
of Veterinary Histology, Blackwell Publishing, Ames, Iowa, 6 th ed., pp.320-349, 2006.

Cat Foot Pad
Monteiro-Riviere NA: Integument. In Eurell J, Frappier B, eds. Dellman’s Textbook of
Veterinary Histology, Blackwell Publishing, Ames, Iowa, 6th ed., pp.320-349, 2006.

Comparative Epidermal Thickness and Number
of Cell Layers From the Back of Nine Species
Species Epidermis Stratum Corneum Number of Cell Layers
(µm) (µm)
Cat 12.97 + 0.93 5.84 + 1.02 1.28 + 0.13
Cow 36.76 + 2.95 8.65 + 1.17 2.22 + 0.11
Dog 21.16 + 2.55 5.56 + 0.85 1.89 + 0.16
Horse 33.59 + 2.16 7.26 + 1.04 2.50 + 0.25
Monkey 26.87 + 3.14 2.05 + 2.30 2.67 + 0.24
Mouse 13.32 + 1.19 2.90 + 0.12 1.75 + 0.08
Pig 51.89 + 1.49 12.28 + 0.72 3.94 + 0.13
Rabbit 10.85 + 1.00 6.56 + 0.37 1.22 + 0.11
Rat 21.66 + 2.23 5.00 + 0.85 1.83 + 0.17
Monteiro-Riviere et al. Interspecies and interegional analysis of the comparative
histological thickness and laser Doppler blood flow measurements at five cutaneous
sites in nine species. Journal of Investigative Dermatology 95:582-586, 1990.

Blood Flow Measurements of Nine Species at
Five Cutaneous Sites
Species BUT EAR HSJ TLJ VAB
Cat 1.82 + 0.59 6.46 + 2.30 1.86 + 0.70 2.39 + 0.35 6.19 + 0.94
Cow 6.03 + 1.84 6.98 + 2.19 5.51 + 2.32 5.49 + 1.49 10.49 + 2.13
Dog 2.21 + 0.67 5.21 + 1.53 5.52 + 1.31 1.94 + 0.27 8.78 + 1.40
Horse 3.16 + 1.22 ----- 6.76 + 1.49 2.99 + 0.86 8.90 + 1.46
Monkey 3.12 + 0.58 20.93 + 5.37 8.49 + 3.28 2.40 + 0.82 3.58 + 0.41
Mouse 3.88 + 0.92 1.41 + 0.48 10.10 + 3.51 20.56 + 4.69 36.85 + 8.14
Pig 3.08 + 0.48 11.70 + 3.02 6.75 + 2.09 2.97 + 0.56 10.68 + 2.14
Rabbit 3.55 + 0.93 8.38 + 1.53 5.38 + 1.06 5.46 + 0.94 17.34 + 6.31
Rat 4.20 + 1.05 9.13 + 4.97 6.22 + 1.47 9.56 + 2.17 11.35 + 5.53
Units=ml/min/100g (mean + SE)
But = buttocks; Ear = pinnae; HSJ = humeroscapular joint; TLJ = thoracolumbar junction;
VAB = ventral abdomen.
Monteiro-Riviere et al. Interspecies and interegional analysis of the comparative histological
thickness and laser Doppler blood flow measurements at five cutaneous sites in nine species.
Journal of Investigative Dermatology 95:582-586, 1990.

Hair Follicle Density
Species Area of Skin Number of Hair
Follicles/cm 2
Human Abdomen 11 + 1
Pig Back 11 + 1
Rat Back 289 + 21
Mouse Back 658 + 38
Hairless Mouse Back 75 + 6
Bronaugh et al. Methods for in vitro percutaneous absorption studies II. Animal
models for human skin. Toxicology and Applied Pharmacology 62, 481-488, 1982.